The goal of this project is to establish the pathophysiology of corneal would healing following freeze injury associated with the use of frozen corneal tissue for lamellar keratoplasty, penetrating keratoplasty, and cryorefractive surgery (keratomileusis, keratophakia, and epikeratophakia). A number of these techniques (cryorefractive surgery) have recently gained popularity in the ophthalmic community and among the general public despite the lack of knowledge of their short and long term impact on corneal tissue. Delay in visual recovery of up to 6 - 18 months with permanent loss of visual acuity has been reported. Presently, the pathogenesis of these corneal clarity problems following freeze injury is unknown. Studies outlined in this proposal provide needed basic information about the role of inflammation, keratocyte repopulation, keratocyte function, endothelial damage, and alterations to the stromal matrix as they relate to corneal clarity following these procedures. We have developed a reproducible rabbit model of microeratome section lamellar keratoplasty which will enable lus to study in detail the clinical (slit lamp biomicroscopy and pachymetry), morphologic (keratocyte cell depth, keratocyte repopulationkinetics, endothelial damage, and alterations to the extracellular matrix), and biochemical (collagen determination and biosynthesis) changes following a standardized freeze injury to the cornea. These studies will evaluate the short term and long term natural history of the effects of freeze injury to the anterior lamellar grafts. By comparing measurements of corneal clarity (slit lamp biomicroscopy and pachymetry), with the morphologic and biochemical measurements, much-needed information about the role of these variables on the post-operative changes in corneal clarity will be obtained. Future studies based on a detailed understanding of the pathophysiologic events following freeze injury will evaluate the pharmocologic intervention (anti-inflammatory drugs, growth factors, fibroblast chemotactic factors, and lathrogens) of trhe cellular and biochemical events which have been offered as remedies for the corneal clarity problems.